Effect of prenatal stress on ɑ5 GABAA receptor subunit gene expression in hippocampus and pilocarpine induced seizure in rats.

The GABAergic synapses go through structural and functional maturation during early brain development. Maternal stress alters GABAergic synapses in developing brain, which are associated with the pathophysiology of neuropsychiatric disorders in adults. The present study aimed to investigate the effect of prenatal restraint stress (PS) on pilocarpine-induced seizure and ɑ5 subunit of γ-amino butyric acid type A (GABAA) receptor expression in hippocampus. Pregnant Wistar rats were subjected to PS at gestational days 15-17 and the pups were examined for susceptibility to seizure and ɑ5 subunit of GABAA receptor expression in hippocampus at postnatal days 14 and 21 (P14 and PND 21). Quantitative real-time PCR was used for evaluating the gene expression in the pups. Pilocarpine was injected intraperitoneally into the pups and seizure behaviors were recorded. The results showed that ɑ5 subunit mRNA expression significantly increased in hippocampus at both the P14 and P21 in the stressed rats. However, ɑ5 subunit level was greater at the P21 than at the P14 in both the groups. Latency of first tonic-clonic seizure significantly decreased in the PS group compared to the control pups. Number and duration of tonic-clonic seizures increased in the PS rats compared to the controls. PS led to an increase in total score of seizure at the P14 and P21. It can be concluded that PS increases the seizure susceptibility and GABAA receptor ɑ5 subunit gene expression in offspring; it is likely that the mechanism of increased seizure susceptibility by PS, at least in part, can increase the GABAA receptor ɑ5 subunit gene expression in hippocampus.